Most animals have the ability to selectively attend to some stimuli while others are ignored. Mechanisms that endow organisms with this capability are of much general interest since malfunctions in these processes induce debilitating pathologies manifested in a variety of circumstances, e.g., when cognitive function is disrupted by aging, in attention deficit/hyperactivity disorders (AD/HD), and when hallucinations associated with schizophrenia are observed. My laboratory studies processes that regulate afferent transmission in the context of motor control. An advantage of this approach is that we are able to directly assess functional consequences of alterations in the efficacy of sensori-motor transmission (evoked movements can be monitored). Specifically, we study a situation where afferent activation will induce a motor response if it occurs during one phase of a motor program, but it will not evoke a response if it occurs during the antagonistic phase. The general goal of our research is to characterize cellular/molecular processes responsible for this type of phasic control. Proposed work will focus on a form of synaptic plasticity that has recently been identified in several loci in the brain. When this plasticity is present, synaptic transmission is a graded function of the baseline membrane potential (i.e., the membrane potential prior to and during afferent activation and spike initiation). As neurons are depolarized, the amount of transmitter that is released per action potential is increased. Proposed experiments will characterize mechanisms that mediate this interesting, but relatively poorly understood type of plasticity. Additionally, we will test a hypothesis that postulates that it can play an important role in regulating sensori-motor transmission during a motor program. Thus during motor programs sensory neurons in our system are rhythmically depolarized via input from central pattern interneurons. We suggest that under normal conditions this input is needed to up-regulate synaptic transmission to make it functional. Consequently, ongoing activity is not easily disrupted. Under more extreme conditions, very strong peripheral activation may induce functional sensori-motor transmission, but a disruption of ongoing activity is more likely to be beneficial under these circumstances. [unreadable] [unreadable] [unreadable]